PT  - JOURNAL ARTICLE
AU  - Chanawee Hirunpattarasilp
AU  - Gregory James
AU  - Felipe Freitas
AU  - Huma Sethi
AU  - Josef T. Kittler
AU  - Jiandong Huo
AU  - Raymond J. Owens
AU  - David Attwell
TI  - SARS-CoV-2 binding to ACE2 triggers pericyte-mediated angiotensin-evoked cerebral capillary constriction
AID  - 10.1101/2021.04.01.438122
DP  - 2021 Jan 01
TA  - bioRxiv
PG  - 2021.04.01.438122
4099  - http://biorxiv.org/content/early/2021/04/01/2021.04.01.438122.short
4100  - http://biorxiv.org/content/early/2021/04/01/2021.04.01.438122.full
AB  - The SARS-CoV-2 receptor, ACE2, is found on pericytes, contractile cells enwrapping capillaries that regulate brain, heart and kidney blood flow. ACE2 converts vasoconstricting angiotensin II into vasodilating angiotensin-(1-7). In brain slices from hamster, which has an ACE2 sequence similar to human ACE2, angiotensin II alone evoked only a small capillary constriction, but evoked a large pericyte-mediated capillary constriction generated by AT1 receptors in the presence of the SARS-CoV-2 receptor binding domain (RBD). The effect of the RBD was mimicked by blocking ACE2. A mutated non-binding RBD did not potentiate constriction. A similar RBD-potentiated capillary constriction occurred in human cortical slices. This constriction reflects an RBD-induced decrease in the conversion of angiotensin II to angiotensin-(1-7). The clinically-used drug losartan inhibited the RBD-potentiated constriction. Thus AT1 receptor blockers could be protective in SARS-CoV-2 infection by reducing pericyte-mediated blood flow reductions in the brain, and perhaps the heart and kidney.Competing Interest StatementThe authors have declared no competing interest.